Western Liaoning of northeastern China is world-renowned for the MesozoicJehol biota, especially for yielding many feathered dinosaurs, primitive birds, mammals and fossilangiosperm. This paper describes a complete sp...Western Liaoning of northeastern China is world-renowned for the MesozoicJehol biota, especially for yielding many feathered dinosaurs, primitive birds, mammals and fossilangiosperm. This paper describes a complete specimen of a symmetrodont mammal with well-preservedhairs and soft tissue from the basal part of the Yixian Formation in the Sihetun area, Beipiao,western Liaoning. It is significant for understanding the morphology, osteology, phylogeny and lifehabits of Mesozoic symmetrodont mammals.展开更多
Axonal myelination is an essential process for normal functioning of the vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. Th...Axonal myelination is an essential process for normal functioning of the vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. This differentiation occurs on a predictable schedule both in culture and during development. However, the timing mechanisms for oligodendrocyte differentiation during normal development have not been fully uncovered. Recent studies have identified a large number of regulatory factors, including cell-intrinsic factors and extracel- lular signals, that could control the timing of oligodendrocyte differentiation. Here we provide a mechanistic and critical review of the timing control of oligodendrocyte differentiation.展开更多
The existence of circular RNAs (circRNAs) was demonstrated over 30 years ago. They did not gain much interest at the time because they appeared to be relatively rare when compared to the abundance of the canonical lin...The existence of circular RNAs (circRNAs) was demonstrated over 30 years ago. They did not gain much interest at the time because they appeared to be relatively rare when compared to the abundance of the canonical linear RNAs. However, more recent evidence suggests that circRNAs are abundant in cells and tissues and possess intriguing biological properties. These recent developments have renewed our interest in this novel class of molecules. This report will provide an overview of circRNAs, discuss how they may modify our understanding of gene regulation and indicate their most likely relevance to health. The circRNAs from viruses, bacteria and archaea are not in the scope of this report, and we focused this review on circRNAs in eukaryotes.展开更多
Oligodendrocytes(OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK(...Oligodendrocytes(OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK(apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYKdeficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.展开更多
Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests that long non-coding RNAs (In...Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests that long non-coding RNAs (IncRNAs) play key roles in regulating cell fate decision and function in various tissues. However, the role of IncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identifed a novel muscle-enriched IncRNA called 'Myolinc (AK142388)', which we functionally characterized in the C2C12 myoblast cell line. Myolinc is predominately localized in the nucleus, and its levels increase upon induction of the differ-entiation. Knockdown of Myolinc impairs the expression of myogenic regulatory factors and formation of multi-nucleated myotubes in cultured myoblasts. Myolinc also regulates the expression of Filipl in a cis-manner. Similar to MyoUnc, knockdown of FiUpl inhi-bits myogenic differentiation. Furthermore, Myolinc binds to TAR DNA-binding protein 43 (TDP-43), a DNA/RNA-binding protein that regulates the expression of muscle genes (e.g. Actal and MyoD). Knockdown of TDP-43 inhibits myogenic differentiation. We also show that Myolinc-TDP-43 interaction is essential for the binding of TDP-43 to the promoter regions of muscle marker genes. Finally, we show that silencing of Myolinc inhibits skeletal muscle regeneration in adult mice. Altogether, our study identifies a novel IncRNA that controls key regulatory networks of myogenesis.展开更多
Dear Editor, Although various components of the Wnt/β-catenin pathway have been investigated, there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation. For inst...Dear Editor, Although various components of the Wnt/β-catenin pathway have been investigated, there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation. For instance, the △Exon3 mutation of β-catenin[14], which stabilizes β-catenin by deletion of the phosphorylation site for the destruction complex, significantly inhibits the differentiation of oligodendrocytes, but knockout of β-catenin also delays it.展开更多
Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate,differentiate,and eventually fuse with injured myofibers.However,the signaling mechanisms that regulate sat...Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate,differentiate,and eventually fuse with injured myofibers.However,the signaling mechanisms that regulate satellite cell homeostasis and function remain less understood.While IKKp-mediated canonical NF-κB signaling has been implicated in the regulation of myogenesis and skeletal muscle mass,its role in the regulation of satellite cell function during muscle regeneration has not been fully elucidated.Here,we report that canonical NF-κB signaling is induced in skeletal muscle upon injury.Satellite cell-specific inducible ablation of IKKβattenuates skeletal muscle regeneration in adult mice.Targeted ablation of IKKβalso reduces the number of satellite cells in injured skeletal muscle of adult mice,potentially through inhibiting their proliferation and survival.We also demonstrate that the inhibition of specific components of the canonical NF-κB pathway causes precocious differentiation of cultured satellite cells both ex vivo and in vitro.Finally,our results highlight that the constitutive activation of canonical NF-κB signaling in satellite cells also attenuates skeletal muscle regeneration following injury in adult mice.Collectively,our study demonstrates that the proper regulation of canonical NF-κB signaling is important for the regeneration of adult skeletal muscle.展开更多
Oligodendrocytes(OLs) are glial cells that form myelin sheaths around axons in the central nervous system(CNS).Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairmen...Oligodendrocytes(OLs) are glial cells that form myelin sheaths around axons in the central nervous system(CNS).Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairment of movement.Understanding the extracellular signals and intracellular factors that regulate OL differentiation and myelination during development can help to develop novel strategies for enhancing myelin repair in neurological disorders.Here,we report that TAPP1 was selectively expressed in differentiating OL precursor cells(OPCs).TAPP1 knockdown promoted OL differentiation and myelin gene expression in culture.Conversely,over-expression of TAPP1 in immature OPCs suppressed their differentiation.Moreover,TAPP1 inhibition in OPCs altered the expression of Erk1/2 but not AKT.Taken together,our results identify TAPP1 as an important negative regulator of OPC differentiation through the Mek/Erk signaling pathway.展开更多
The ex-copula penile dorsiflexion reflex(PDFR)is an established measure of sexual dysfunction in male rat models of spinal cord injury.Although the PDFR after complete spinal transection is well described,information ...The ex-copula penile dorsiflexion reflex(PDFR)is an established measure of sexual dysfunction in male rat models of spinal cord injury.Although the PDFR after complete spinal transection is well described,information regarding the more clinically relevant incomplete spinal contusion injury model is limited.This study examined,using two-dimensional(2D)kinematic analysis,the relationship between the PDFR and degree of white matter sparing(WMS).Male Wistar rats received a T9 contusion with varying degrees of impactor forces.Weekly kinematic recordings of the PDFR were made 3-8 weeks postinjury.Sexual reflex components examined included maximum angle of penile dorsiflexion,total penile event duration,and penile ascent speed.Post hoc comparison between animals grouped based upon injury severity(moderate-severe:13.33%-17.15%WMS vs moderate:20.85%-33.50%WMS)ndicated PDFR effects.Specifically,the numbers of animals with more moderate contusions having data points above the median n both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe njuries.Total penile event duration was also affected but only at more chronic time points(6-8 weeks).Thus,2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.展开更多
Neurotrophins are a family of proteins that regulate neural survival, development, function and plasticity in the central and the peripheral nervous system. There are four neurotrophins: NGF, BDNF, NT-3 and NT-4. Amo...Neurotrophins are a family of proteins that regulate neural survival, development, function and plasticity in the central and the peripheral nervous system. There are four neurotrophins: NGF, BDNF, NT-3 and NT-4. Among them, BDNF is mostly studied in the taste system due to its high expression. Recent studies have shown BDNF play an important role in the developmental and mature taste system, by regulating survival of taste cells and geniculate ganglion neurons, and maintaining and guiding taste nerve innervations. These studies imply BDNF has great potentialities for therapeutic usage to enhance sensory regeneration following nerve injury, with aging, and in some neurodegenerative diseases.展开更多
Myelin is an evolutionarUy novel and important structure for the proper functioning of the vertebrate nervous system. In the central nervous system (CNS), the myelin sheath is elaborated by oligodendrocytes, and is ...Myelin is an evolutionarUy novel and important structure for the proper functioning of the vertebrate nervous system. In the central nervous system (CNS), the myelin sheath is elaborated by oligodendrocytes, and is composed of multiple layers of specialized cell membrane wrapping around axons with periodic interruptions at the nodes of Ranvier. The major function of the myelin sheath is to provide ionic insulation to ensure rapid and saltatory conduction of electrical pulses along axons. In addition, myelin provides neurotrophic support for axons, as they become increasingly dependent on myelin-derived signals for survival. Despite the importance of myelin in the functioning of the CNS, oligodendrocytes are particularly susceptible to genetic and environmental perturbations, and demyelination can be triggered by many pathological conditions including traumatic injury, autoimmune disease (multiple sclerosis, MS), heavy metal toxicity, and hypoxia. Loss of myelin sheaths in the CNS not only results in the compromised conduction of electrical signals, but also causes progressive degeneration of axons and ultimately neuronal loss. Spontaneous myelin repair from immature oligodendrocyte progenitor cells (OPCs) is not effective in demyelinating lesions, due either to the absence of stimulatory developmental signals that are no longer produced in the adult environment, or to the presence of inhibitory factors peculiar to this environment.展开更多
文摘Western Liaoning of northeastern China is world-renowned for the MesozoicJehol biota, especially for yielding many feathered dinosaurs, primitive birds, mammals and fossilangiosperm. This paper describes a complete specimen of a symmetrodont mammal with well-preservedhairs and soft tissue from the basal part of the Yixian Formation in the Sihetun area, Beipiao,western Liaoning. It is significant for understanding the morphology, osteology, phylogeny and lifehabits of Mesozoic symmetrodont mammals.
基金supported by grants from the National Basic Research Development Program of China(2013CB5313002012CB910402)+4 种基金the National Natural Science Foundation of China(31071879, 31000488)Major Science and Technology Projects of Zhejiang Province, China(2011C13030)the Natural Science Foundation of Zhejiang Province, China(Z2100730)the NiH(R01-NS37717)National Multiple Sclerosis Society (RG3276)
文摘Axonal myelination is an essential process for normal functioning of the vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. This differentiation occurs on a predictable schedule both in culture and during development. However, the timing mechanisms for oligodendrocyte differentiation during normal development have not been fully uncovered. Recent studies have identified a large number of regulatory factors, including cell-intrinsic factors and extracel- lular signals, that could control the timing of oligodendrocyte differentiation. Here we provide a mechanistic and critical review of the timing control of oligodendrocyte differentiation.
文摘The existence of circular RNAs (circRNAs) was demonstrated over 30 years ago. They did not gain much interest at the time because they appeared to be relatively rare when compared to the abundance of the canonical linear RNAs. However, more recent evidence suggests that circRNAs are abundant in cells and tissues and possess intriguing biological properties. These recent developments have renewed our interest in this novel class of molecules. This report will provide an overview of circRNAs, discuss how they may modify our understanding of gene regulation and indicate their most likely relevance to health. The circRNAs from viruses, bacteria and archaea are not in the scope of this report, and we focused this review on circRNAs in eukaryotes.
基金supported by the National Natural Sciences Foundation of China (31471955)the Natural Science Foundation of Zhejiang Province, China (LY17C090006+1 种基金 Q16C090017 LY18H090014)
文摘Oligodendrocytes(OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK(apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYKdeficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
文摘Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests that long non-coding RNAs (IncRNAs) play key roles in regulating cell fate decision and function in various tissues. However, the role of IncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identifed a novel muscle-enriched IncRNA called 'Myolinc (AK142388)', which we functionally characterized in the C2C12 myoblast cell line. Myolinc is predominately localized in the nucleus, and its levels increase upon induction of the differ-entiation. Knockdown of Myolinc impairs the expression of myogenic regulatory factors and formation of multi-nucleated myotubes in cultured myoblasts. Myolinc also regulates the expression of Filipl in a cis-manner. Similar to MyoUnc, knockdown of FiUpl inhi-bits myogenic differentiation. Furthermore, Myolinc binds to TAR DNA-binding protein 43 (TDP-43), a DNA/RNA-binding protein that regulates the expression of muscle genes (e.g. Actal and MyoD). Knockdown of TDP-43 inhibits myogenic differentiation. We also show that Myolinc-TDP-43 interaction is essential for the binding of TDP-43 to the promoter regions of muscle marker genes. Finally, we show that silencing of Myolinc inhibits skeletal muscle regeneration in adult mice. Altogether, our study identifies a novel IncRNA that controls key regulatory networks of myogenesis.
基金supported by the National Basic Research Development Program of China (2013CB531303, 2012CB910402)the National Natural Science Foundation of China (31101642, 31372150)+1 种基金the Science and Technology Key Project of Zhejiang Province, China (2011C13030)the National Institutes of Health, USA (R01-NS37717)
文摘Dear Editor, Although various components of the Wnt/β-catenin pathway have been investigated, there are conflicting reports on the roles of Wnt/β-catenin signaling in oligodendrogenesis and differentiation. For instance, the △Exon3 mutation of β-catenin[14], which stabilizes β-catenin by deletion of the phosphorylation site for the destruction complex, significantly inhibits the differentiation of oligodendrocytes, but knockout of β-catenin also delays it.
文摘Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate,differentiate,and eventually fuse with injured myofibers.However,the signaling mechanisms that regulate satellite cell homeostasis and function remain less understood.While IKKp-mediated canonical NF-κB signaling has been implicated in the regulation of myogenesis and skeletal muscle mass,its role in the regulation of satellite cell function during muscle regeneration has not been fully elucidated.Here,we report that canonical NF-κB signaling is induced in skeletal muscle upon injury.Satellite cell-specific inducible ablation of IKKβattenuates skeletal muscle regeneration in adult mice.Targeted ablation of IKKβalso reduces the number of satellite cells in injured skeletal muscle of adult mice,potentially through inhibiting their proliferation and survival.We also demonstrate that the inhibition of specific components of the canonical NF-κB pathway causes precocious differentiation of cultured satellite cells both ex vivo and in vitro.Finally,our results highlight that the constitutive activation of canonical NF-κB signaling in satellite cells also attenuates skeletal muscle regeneration following injury in adult mice.Collectively,our study demonstrates that the proper regulation of canonical NF-κB signaling is important for the regeneration of adult skeletal muscle.
基金supported by the National Natural Sciences Foundation of China (31471955 and 31372150)the National Basic Research Development Program (973 Program) of China (2013CB531300)
文摘Oligodendrocytes(OLs) are glial cells that form myelin sheaths around axons in the central nervous system(CNS).Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairment of movement.Understanding the extracellular signals and intracellular factors that regulate OL differentiation and myelination during development can help to develop novel strategies for enhancing myelin repair in neurological disorders.Here,we report that TAPP1 was selectively expressed in differentiating OL precursor cells(OPCs).TAPP1 knockdown promoted OL differentiation and myelin gene expression in culture.Conversely,over-expression of TAPP1 in immature OPCs suppressed their differentiation.Moreover,TAPP1 inhibition in OPCs altered the expression of Erk1/2 but not AKT.Taken together,our results identify TAPP1 as an important negative regulator of OPC differentiation through the Mek/Erk signaling pathway.
文摘The ex-copula penile dorsiflexion reflex(PDFR)is an established measure of sexual dysfunction in male rat models of spinal cord injury.Although the PDFR after complete spinal transection is well described,information regarding the more clinically relevant incomplete spinal contusion injury model is limited.This study examined,using two-dimensional(2D)kinematic analysis,the relationship between the PDFR and degree of white matter sparing(WMS).Male Wistar rats received a T9 contusion with varying degrees of impactor forces.Weekly kinematic recordings of the PDFR were made 3-8 weeks postinjury.Sexual reflex components examined included maximum angle of penile dorsiflexion,total penile event duration,and penile ascent speed.Post hoc comparison between animals grouped based upon injury severity(moderate-severe:13.33%-17.15%WMS vs moderate:20.85%-33.50%WMS)ndicated PDFR effects.Specifically,the numbers of animals with more moderate contusions having data points above the median n both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe njuries.Total penile event duration was also affected but only at more chronic time points(6-8 weeks).Thus,2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.
文摘Neurotrophins are a family of proteins that regulate neural survival, development, function and plasticity in the central and the peripheral nervous system. There are four neurotrophins: NGF, BDNF, NT-3 and NT-4. Among them, BDNF is mostly studied in the taste system due to its high expression. Recent studies have shown BDNF play an important role in the developmental and mature taste system, by regulating survival of taste cells and geniculate ganglion neurons, and maintaining and guiding taste nerve innervations. These studies imply BDNF has great potentialities for therapeutic usage to enhance sensory regeneration following nerve injury, with aging, and in some neurodegenerative diseases.
文摘Myelin is an evolutionarUy novel and important structure for the proper functioning of the vertebrate nervous system. In the central nervous system (CNS), the myelin sheath is elaborated by oligodendrocytes, and is composed of multiple layers of specialized cell membrane wrapping around axons with periodic interruptions at the nodes of Ranvier. The major function of the myelin sheath is to provide ionic insulation to ensure rapid and saltatory conduction of electrical pulses along axons. In addition, myelin provides neurotrophic support for axons, as they become increasingly dependent on myelin-derived signals for survival. Despite the importance of myelin in the functioning of the CNS, oligodendrocytes are particularly susceptible to genetic and environmental perturbations, and demyelination can be triggered by many pathological conditions including traumatic injury, autoimmune disease (multiple sclerosis, MS), heavy metal toxicity, and hypoxia. Loss of myelin sheaths in the CNS not only results in the compromised conduction of electrical signals, but also causes progressive degeneration of axons and ultimately neuronal loss. Spontaneous myelin repair from immature oligodendrocyte progenitor cells (OPCs) is not effective in demyelinating lesions, due either to the absence of stimulatory developmental signals that are no longer produced in the adult environment, or to the presence of inhibitory factors peculiar to this environment.